Written by Taylor Woosley, Staff Writer. 9-week supplementation with Synbiotic 2000 resulted in a significant reduction of levels of IL-12/ IL23p40, sICAM-1, and TGF-β3 in children with ADHD from baseline to follow-up compared to placebo (p = 0.020).

ADHD - Brain HealthAttention-deficit/hyperactivity disorder (ADD) is characterized by persisting and impairing symptoms of age-inappropriate inattention and/or hyperactivity/impulsivity1. Studies suggest that the bidirectional relationship existent between the gut microbiome and the central nervous system (CNS) is involved in diverse neuropsychiatric diseases in children and adults2. Dysbiosis, an imbalance of microbial species, may produce oxidative stress that affects neuron cell and neurotransmitters related to ADHD3.

Dietary intake and supplementation may have an important effect on the gut microbiota, the composition of which may be related to the short-chain fatty acids (SCFAs) produced by the metabolism of dietary ingredients4. ADHD is linked to various neuromodulators (i.e. serotonin and dopamine) and involves dysfunction in both cognitive and socio-affective brain networks, with the state of the microbiome playing a significant role in mental health5. Previous research on Synbiotic 2000, a product containing 3 lactic acid bacilli and 4 dietary fibers, has shown positive effects on emotion regulation in ADHD patients6.

Yang et al. conducted a randomized controlled study to explore the effects of Synbiotic 2000 on concentrations of plasma immune activity markers and SCFAs in ADHD. Participants (n = 248) were included if they had a prior ADHD diagnosis, were between the age of 5-55 years old, and, if treated, were currently on a stable pharmacological treatment, were not on antibiotic treatment in the last 6 weeks and did not have a gastrointestinal diagnosis. In parallel, healthy adult subjects without ADHD (n=72) were recruited during the same period. Subjects were randomly allocated to either the Synbiotic 2000 group or placebo. Synbiotic 2000 consisted of lyophilized 4 x 1011 CFU of three lactic acid bacteria and 2.5 g each of the fermentable fibers beta-glucan, inulin, pectin, and resistant starch per dose. The placebo group was given a maltodextrin sachet. Both groups were informed to follow the treatment with one dose per day. All participants were assessed at baseline and post-treatment (within 2 weeks after the 9-week intervention was completed) through interviews and questionnaires regarding psychiatric and GI symptoms. Furthermore, subjects gave non-fasted blood samples at baseline and follow-up.

A total of 182 participants completed the 9-week intervention, with 156 subjects providing both blood samples. The control group was assessed at one time-point and 61 provided blood samples. A total of 24 plasma immune activity markers such as CRP, serum amyloid A, IL-6, IL-10, IL-12, TNF-α, and vascular endothelial growth factor A were measured. Additionally, SCFAs were analyzed, with the exclusion of isobutyric, valeric, and caproic acid. Mann-Whitney U tests were used to analyze the differences in analyte levels between diagnosis groups (control versus ADHD subject), age groups, medication groups, and sexes. Spearman’s rank correlation was utilized to assess statistical relationships between two analytes. Significant findings of the study are as follows:

  • For children currently on ADHD medication, Synbiotic 2000 resulted in a significant reduction of IL-12/IL-23p40 (99% CI: -180, -0.005, p = 0.0070) and a suggestive reduction in sICAM-1 levels (95% CI: -0.547, -0.030, p = 0.030) compared to placebo.
  • For children and adults not currently on ADHD medication, Synbiotic 2000 suggestively increased levels of VEGF-A (children: 95% CI: 0.054, 0.644, p = 0.024; and adults: 95% CI: 0.007, 0.368, p = 0.043).
  • Synbiotic 2000, compared to placebo, suggestively increased propionic acid concentrations in children with ADHD (95% CI: 0.006, 0.699, p = 0.046).

Results of the study show that 9-week supplementation of Synbiotic 2000 in children suggestively reduced pro-inflammatory IL-12/IL-23p40 levels after age-group-stratified analyses. However, there was no other statistically significant overall effect of Synbiotic 2000 compared to placebo on any analyte analyzing all pediatric and adult participants as one group. Study limitations include the inability to analyze the four healthy controls for children due to the small sample size, the lack of information regarding specific drug names and drugs targeting inflammation, and the potential of diet or diet supplements used during the intervention to possibly conceal the effects of Synbiotic 2000.

Source: Yang, Liu L., Miranda Stiernborg, Elin Skott, Jingjing Xu, Yujiao Wu, Rikard Landberg, Samsul Arefin et al. “Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD—A Randomized Controlled Trial.” Nutrients 15, no. 5 (2023): 1293.

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Posted April 17, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Rubia K, Westwood S, Aggensteiner PM, Brandeis D. Neurotherapeutics for Attention Deficit/Hyperactivity Disorder (ADHD): A Review. Cells. Aug 21 2021;10(8)doi:10.3390/cells10082156
  2. Checa-Ros A, Jeréz-Calero A, Molina-Carballo A, Campoy C, Muñoz-Hoyos A. Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications. Nutrients. Jan 16 2021;13(1)doi:10.3390/nu13010249
  3. Sukmajaya AC, Lusida MI, Soetjipto, Setiawati Y. Systematic review of gut microbiota and attention-deficit hyperactivity disorder (ADHD). Ann Gen Psychiatry. Feb 16 2021;20(1):12. doi:10.1186/s12991-021-00330-w
  4. Jung TH, Hwang HJ, Han KS. Correlation of attention deficit hyperactivity disorder with gut microbiota according to the dietary intake of Korean elementary school students. PLoS One. 2022;17(9):e0275520. doi:10.1371/journal.pone.0275520
  5. Mathee K, Cickovski T, Deoraj A, Stollstorff M, Narasimhan G. The gut microbiome and neuropsychiatric disorders: implications for attention deficit hyperactivity disorder (ADHD). J Med Microbiol. Jan 2020;69(1):14-24. doi:10.1099/jmm.0.001112
  6. Yang LL, Stiernborg M, Skott E, et al. Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial. Nutrients. Mar 6 2023;15(5)doi:10.3390/nu15051293